This application pertains to the art of magnetic separation, and more particularly to magnetic separation of biological materials.
The invention is particularly applicable to analysis of biological substances and will be described with particular reference thereto, although it will be appreciated that the invention has broader applications such as analysis of any substance containing magnetically sensitive particles, or particles which have been made susceptible to magnetic influence.
Ferrography is a method of particle separation relying on interaction between an external magnetic field and magnetic dipole moments of particles. The first published use of ferrography was in 1972 by Siefert and Westcott, and that use was particularly for industrial applications. Such industrial applications included monitoring of wear debris in oil or grease lubricants, and hydraulic systems, as well as gas stream monitoring of non-lubricant wash components. On-line systems have been developed for these industrial applications. Ferrography has proven itself in early wear detection and in prescribing preventative maintenance for non-catastrophic down time of man-made machines.
To date, ferrography has made only limited impact in bio-medical applications. Experience consists primarily of analysis of wear in natural and in prosthetic joints. Some experience of magnetic analysis of erythrocytes in white blood cell separations, and that of a few bacterial strains have been reported. The use of magnetic fields, such as in high-gradient magnetic separators ("HGMS"), for the separation of cells has been described and applied with various approaches.
Filters utilizing the principle of HGMS have been specifically noted to retain deoxygenated or oxidized (methemoglobin) erythrocytes while permitting other blood components to pass through. For other cells, such as certain leucocytes and other cellular classes which lack intrinsic magnetic properties, it has been demonstrated that they can be separated by first allowing them to phagocytize magnetic particles, bind magnetic microspheres, rosette erythrocytes containing paramagnetic methemoglobin, or be infected with malarial parasites (used for erythrocytes).
A further method of conferring magnetic susceptibility to cells or biological molecules is through antibodies and bio-molecules coupled to a highly magnetic protein containing iron or paramagnetic elements, such as ferritin. It is possible to separate immunoferritin-coated cells from a mixed population.
Many problems are encountered when attempting to apply industrial-type ferrography to the area of biological fluid analysis. Many problems are associated with analysis of magnetically low susceptible biological particles in the conventional ferrographic technique due to less than optimal fluid dynamics, low magnetic field gradients, and the lack of adequate magnetizers. Further problems are found in that often times a sample of biological material must be isolated from the outside as it often contains transmittable diseases.
The present invention contemplates a new and improved magnetic field separation analysis system which overcomes all of the above-referred problems, and others, and provides a means for analysis of biological fluids which is simple, economical and safe.